PD16 The application of transport disc distraction osteogenesis (TDDO) for mandibular reconstruction after composite mandibulectomy

Oral and Symposium abstracts, Saturday 19 May Saturday 19 May

08:00 12:00

Session 3 Panel discussion 4

Tissue engineering and transplantation in oral cancer

81 reconstruction with frozen autologous mandible to evaluate the feasibility of this technique, the capability of periosteum to rivitalize the bone and the definitive mandibular integration and review other reconstructive techniques reported in recent literature (bone growth factors, BMP etc). PD15 Bone tissue engineering in cancer patients perspectives and limitations H. Schliephake *. Georg-August University, Germany

B. Devauchelle1 *, B. Lengele2 , L. Badet3 , C. Moure1 , S. Dakpe1 , S. Cremades1 , E. Morellon3 , S. Testelin1 , J.M. Dubernard3 . 1 CHU Amiens, France;, 2 Universit´ e Catholique de Louvain, Belgium, 3 Hospital E. Herriot, France Traumatic, malformative or tumoral, the disfiguration is not univocal. Here the priority is the survival, there the reference is the comparison, or sometimes a complete restitution is requested. Front of disfiguration, the allotransplantation is not only a surgical answer, it is a new proposal for treatment with imposed risks and penibility of a medical immunosuppressive treatment which is obviously impossible in case of malignant tumors. It is also necessary to discuss about indications of allotransplantation of composite tissue for face reconstruction: regarding its topography: if it is partial (for which area? If they are not reconstructible by other conventional procedures) or full face, regarding the etiology: after trauma, malformation or for huge benign tumor. The authors analyzed all different cases and discuss other specific questions like age, immunologic particular cases and also that for each pathology. PD14 Reimplantation of frozen autologous mandibular bone covered by radial periosteal free flap for immediate reconstruction in oral cancer surgery: preliminary experience G. Spriano *, V. Manciocco, R. Pellini. National Cancer Institute “Regina Elena”, Italy Since the beginning of the 20th century, mandibular reconstruction has been one of the biggest challenges for head and neck surgeons. The purpose of mandibular reconstruction is to regain normal functions of mastication, deglutition, and speech, while attempting to reconstitute the contour of the lower third of the face. Size and location of a potential reconstruction site are critical factors in determining the type of intervention to be employed. Vascularized autogenous bone grafts are currently the most common methods used for mandibular reconstruction. In case of extensive tumor infiltration of the bone, a segmental resection of the mandible with safe margins is mandatory and a composite osteocutaneous microvascular free flap is the gold standard for reconstruction even if it exposes the patients to additional complications in the distant donor site of bone harvest. When the mandible does not present massive involvement, the possibility of reconstruction with the same sterilized bone as an autologous implant is attractive because that reconstruction would avoid the need to harvest and mold a bone from a distant donor site with possible related complication. Vascular supply to the frozen neo-mandible is ensured by the periosteal layer of a microvascular radial periosteal fasciocutaneous free flap, placed to envelope the bone and cover the surgical defect. Surgical procedure consists in a segmental mandibulectomy followed by adequate detachment to the mandible of soft tissues, teeth and macroscopic infiltration, and sterilization liquid nitrogen about 10 minutes. The mandible is repositioned in the original site, fixed by titanium plates and completely covered by a periosteal fasciocutaneous forearm free flap. The authors present our preliminary experience in mandibular

Bone tissue engineering uses either growth factors on a variety of carriers or osteogenic cells seeded onto an even larger number of different materials. The former approach has been successful in preclinical animal studies has shown ambiguous results in clinical applications or required extremely high dosages compared to the natural content of growth factors in bone. This extensive dosage is considered to be necessary due to insufficient release characteristics of carriers used. The development of advanced carrier technology for bone growth factors is thus one of the challenges in bone tissue engineering. The use of osteogenic cells seeded onto biomaterials and implanted into skeletal defects has been employed alternatively. However, despite a decade of experimental evaluation a number of unresolved questions remain. Poor cell survival and inferior bone specific cellular activity after transplantation have to be considered as reasons for unsatisfactory results which may occur due to premature differentiation and subsequent growth cessation, dedifferentiation and/or poor revascularization in vivo. This problem is even more relevant in extensive post ablative defects or following radiation therapy. More sophisticated approaches in the use of osteogenic cells will be necessary by enhancing the osteogenic activity of seeded cells and improving vascularization after implantation through the supplementary use of growth factors and bioactive scaffolds to successfully regenerate bone in a clinically relevant dimension. Finally, possible side effects of proliferative agents and stem cells on dormant or residual tumour cells have to be taken into account. In conclusion, skeletal reconstruction using bone tissue engineering approaches in cancer patients and has to deal with unfavourable conditions and may be limited by the biology the underlying disease. PD16 The application of transport disc distraction osteogenesis (TDDO) for mandibular reconstruction after composite mandibulectomy D.B. Chepeha *, T.N. Teknos, M.E. Prince, J.S. Moyer, A.G. Sacco. A. Alfred Taubman Health Center, USA The associated morbidities and reduction in quality of life following reconstruction of the mandibular defect affected by the quality of the reconstruction. In an attempt to improve patient outcome, alternative treatments such as distraction osteogenesis may be an option. The goal of this technology is to restore boney continuity through the use of in situ bone in an attempt to create an anatomically correct regenerate that would be superior to bone grafting or revascularized free tissue transfer. Distraction osteogenesis involves a three step process in which bone adjacent to the defect is osteotomized, gradually opened (distracted) with the aid of a mechanical device (transport disc) followed by formation of new bone with subsequent consolidation. Previous work involving animal models, human case reports, and small case series have shown encouraging results regarding the translation of distraction osteogenesis technology from an animal model to human application, with particular success in the unradiated setting. The major challenge surrounding the use of this technology in head and neck oncologic reconstruction will be the effect of radiation therapy on the regenerate bone in patients who have

Oral abstracts

PD13 Tumoral disfigurations and allotransplantation

82 previously received or will require radiation as part of their treatment paradigm. This challenge is common to most tissue engineering technology. While distraction osteogenesis provides an attractive alternative for reconstruction of mandibular defects, larger studies of human populations will be required to determine its role in the treatment paradigm for reconstruction of mandibular defects.

Oral and Symposium abstracts, Saturday 19 May laboratories and will be presented. This data will permit clinical researchers the opportunity to systematically measure the function of patients at various stages of their treatment and to develop new interventions directed toward improvements in and recovery of aesthetics, mastication, swallowing, and speaking. S15 New perspectives on tumor biology oropharynx

Symposium American Head and Neck Society

Challenges in an integrated approach to treatment and rehabilitation of cancers of the oral cavity S13 New perspectives on treatment outcome and quality of life E.A. Weymuller *. University of Washington Medical Center, USA Given the current therapeutic options for head and neck (H&N) cancer, it is impossible to avoid treatment-related side effects. These outcomes have a direct impact on the day-to-day ability of our patients to enjoy their existence, ie, their quality of life (QOL). In comparison to more common cancers, patients treated for H&N cancer are more impaired with respect to QOL and have triple the expected suicide rate among the US population. For these reasons investigations in QOL are relevant and important. The intent of this presentation is to highlight outcome information regarding the impact of the increased use of chemoradiation. The presentation will also focus on what has been learned in the steadily expanding analysis of QOL in HN cancer. The specific goals of the presentation are to highlight the importance of patient reported data in the analysis of outcomes and the use of QOL instruments in active patient care. It is recommended that multi-institutional trials should add QOL data as a pretreatment variable. Keywords: dysphagia, suicide, depression, quality of life S14 Oral cavity reconstruction, an integrative approach with prosthodontics T.A. Day *, B.K. Davis, J.D. Hornig, J.D. Skoner, M.B. Gillespie, B.M. Martin-Harris, M. Brodsky, A.K. Sharma. Hollings Cancer Center-MUSC, USA Oral cancer is most commonly treated with surgical extirpation and associated reconstruction and rehabilitation with primary goals of curative treatment while optimizing functional outcomes and quality of life. Disorders of oral health, mastication, speech production, and swallowing contribute to high functional morbidity in this patient population. Worldwide, many obstacles prevent an individual oral cancer patient from receiving a combination of surgical treatment, surgical reconstruction, prosthetic rehabilitation, in addition to speech, swallowing, and masticatory rehabilitation. At the MUSC/HCC Head and Neck Tumor Program, head and neck extirpative surgeons, reconstructive surgeons, maxillofacial prosthodontists, dental oncologists, speech pathologists, radiation oncologists, and researchers are involved in multidisciplinary clinical care and research studies to enhance the care of current and future oral cancer patients. A continuum of clinical care and clinical research has been established not only to facilitate rapid and appropriate functional rehabilitation of patients, but also to provide patients and providers with empirical evidence regarding the expected outcomes from various surgeries and other cancer treatments. Standardized methods for the quantification of baseline and treatment-related functional impairment have been developed and tested in these clinical

oral cavity and

T.E. Carey *. University of Michigan, USA Organ sparing therapies are developing as an alternative to radical surgery for advanced head and neck cancer. Following observations from the VA Larynx trial that chemotherapy and radiation can be as effective as surgery and radiation for advanced cancers of the larynx, numerous protocols have been and are being developed to improve response rates, survival and quality of life. However, for those patients who fail to respond, surgery is still required, and many patients regardless of treatment still fail to respond and die of their head and neck cancer. Our protocols for advanced larynx and oropharyngeal cancer using induction chemotherapy, followed by concurrent chemotherapy and radiation in responders (i.e. 50% reduction in size of the primary tumor) or surgery for non-responders has allowed our group to demonstrate increased survival at both sites. However, the same protocol was not effective for oral cancer patients. To better understand the mechanisms of tumor resistance to treatment, we have analyzed patient characteristics and biomarkers in pretreatment biopsies. Using the information gained from these tissues we have then developed and tested hypotheses in the laboratory using our panel of head and neck squamous cell carcinoma cell lines developed from our patients. Together these sources of information allow us to identify factors that are responsible for resistance to therapy and to devise novel strategies to overcome resistance in patients who would otherwise fail to respond. Our results have shown that p53 and Bcl-XL expression predict response to treatment and survival. Novel agents to target Bcl-xL can target the most resistant tumor cells in in vitro and in vivo models in the laboratory. High risk HPV is becoming an important etiologic factor in oropharyngeal cancer especially among younger patients. HPV, EGFR expression, and smoking status are all factors that determine outcome in oropharyngeal cancer and suggest that the same markers might allow us to understand why oral cancers are less likely to respond to organ sparing therapy. The results of such studies may allow for more specific individualized treatment that will reduce morbidity for those patients with highly responsive tumors and allow more effective therapy for those who would otherwise succumb to their tumors. S16 Multidisciplinary treatment and the development of future strategies: the cancer biologist as a team member G.T. Wolf *, T.E. Carey, C.R. Bradford, J. Lee, T.E. Teknos, D.B. Chepeha, M.E. Prince, J. Moyer, A. Eisbruch, F. Worden, S. Urba, S. Duffy. University of Michigan, USA Treatment paradigms in head and neck oncology are changing at an ever increasing rate. Traditional oncologic principles are being challenged as prognostic markers of biologic behavior are identified and new pharmacogenetic targets useful for inhibiting tumor growth are discovered. Recently, concurrent CT-XRT in patients with advanced laryngeal or oropharyngeal cancers has improved local (L/R) tumor control, organ preservation and survival compared to radiation alone. Whether such an approach could be effective in patients with advanced oral cavity carcinoma is unclear. Surgical salvage for L/R failures for such patients is difficult and often unsuccessful. Appropriate early selection of patients who have chemo-